Phosphotyrosyl phosphatase activator facilitates Miranda localization through dephosphorylation in dividing neuroblasts

Abstract

The mechanism for the basal targeting of the Miranda (Mira) complex during the asymmetric division of Drosophila neuroblasts (NBs) is yet to be fully understood. We have identified conserved Phosphotyrosyl Phosphatase Activator (PTPA) as a novel mediator for the basal localization of the Mira complex in larval brain NBs. In ptpa NBs, Mira remains cytoplasmic during early mitosis where its basal localization is delayed until anaphase. Detailed analyses indicate that PTPA acts independently of, and prior to, aPKC activity to localize Mira. Mechanistically, our data show that the phosphorylation status of the Thr591 (T591) residue determines the subcellular localization of Mira and that PTPA facilitates the dephosphorylation of T591. Furthermore, PTPA associates with the Protein Phosphatase 4 complex to mediate Mira localization. Based on these results, a two-step process for Mira basal localization during NB division is revealed where PTPA/PP4-mediated cortical association followed by apical aPKC-mediated basal restriction.